Unadjusted Hazard Ratio For Death Research Articles

Outcomes for patients with high-risk endometrial cancer undergoing sentinel lymph node assessment versus full lymphadenectomy

ObjectiveThe objective of this study was to determine the progression free survival (PFS) and overall survival (OS) among patients with high-risk endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping and dissection compared to patients who underwent pelvic +/− para-aortic lymphadenectomy (LND). MethodsPatients with newly diagnosed high-risk EC were identified. Inclusion criteria included patients who underwent primary surgical management from January 1, 2014 to September 1, 2020 at our institution. Patients were categorized into either the SLN or LND group based on their method of planned lymph node assessment. Patients in the SLN group had dye injected followed by successful bilateral lymph node mapping, retrieval, and processing per our institutional protocol. Clinicopathological and follow-up data were extracted from patient's medical records. The t-test or Mann-Whitney test was used to compare continuous variables and Chi-squared or Fisher's exact test were used for categorical variables. Progression-free survival (PFS) was calculated from the date of initial surgery to the date of progression, death, or last follow-up. Overall survival (OS) was calculated from the date of surgical staging to the date of death or last follow-up. Three-year PFS and OS were calculated using the Kaplan-Meier method, and the log-rank test was used to compare cohorts. Multivariable Cox regression models were used to assess the relationship between nodal assessment cohort and OS/PFS while adjusting for age, adjuvant therapy, and surgical approach. A result was considered statistically significant at the p < 0.05 level of significance and all statistical analysis was done using SAS version 9.4 (SAS Institute, Cary, NC). ResultsOut of 674 patients diagnosed with EC during the study period, 189 were diagnosed with high-risk EC based on our criteria. Forty-six (23.7%) patients underwent SLN assessment and 143 (73.7%) underwent LND. No difference was observed between the two groups in regards to age, histology, stage, body mass index, tumors myometrial invasion, lymphovascular space invasion, or peritoneal washing positivity. Patients in the SLN group underwent robotic-assisted procedures more frequently than those in the LND group (p < 0.0001). The three-year PFS rate was 71.1% (95% CI 51.3–84.0%) in the SLN group and 71.3% (95% CI 62.0–78.6%) in the LND group (p = 0.91). The unadjusted hazard ratio (HR) for recurrence in the SLN versus LND group was 1.11 (95% CI 0.56–2.18; p = 0.77), and after adjusting for age, adjuvant therapy, and surgical approach, the HR for recurrence was 1.04 (95% CI 0.47–2.30, p = 0.91). The three-year OS rate was 81.1% (95% CI 51.1–93.7%) in the SLN group and 95.1% (95% CI 89.4–97.8%) in the LND group (p = 0.009). Although the unadjusted HR for death was 3.74 in the SLN vs LND group (95% CI 1.39–10.09; p = 0.009), when adjusted for age, adjuvant therapy, and surgical approach, it was no longer significant with a HR of 2.90 (95% CI 0.94–8.95, p = 0.06). ConclusionsThere was no difference in three-year PFS in patients diagnosed with high-risk EC who underwent SLN evaluation compared to those who underwent full LND in our cohort. The SLN group did experience shorter unadjusted OS; however, when adjusting for age, adjuvant therapy and surgical approach, there was no difference OS in patients who underwent SLN compared to LND.

Impact of Length of Diabetes in Donor Hearts on Post-Transplant Survival

<h3>Purpose</h3> Consideration of co-morbid conditions in prospective heart donors may impact the decision to accept a cardiac allograft for transplantation. Diabetes is a known risk factor for cardiovascular disease. We sought to investigate the potential impact of donor diabetes duration on post-transplant survival. <h3>Methods</h3> All adult patients who received a heart transplant from a donor with diabetes registered in the UNOS database from 1/1/2010 - 6/1/2021 were analyzed. Heart transplant recipients were stratified by duration of donor diabetes diagnosis 0-5 years (n=763), 6-10 years (n=241), >10 years (n=349). Baseline characteristics were compared using Mann-Whitney U test and Chi-square test as appropriate. Kaplan-Meier survival analysis was performed for 60 months post-transplantation. <h3>Results</h3> There was no difference in survival post transplant at 60 months among heart transplant recipients who received donor hearts from patients with diabetes for 0-5, 6-10, or >10 years at time of transplant, p=0.930. After a follow up of 60 months the unadjusted hazard ratio for death was 0.975, (95% CI, .344-1.53); p = 0.402, following adjustment, the hazard ratio was 0.975, (95% CI,.836 to 1.14); p = 0.904. Hearts from donors with shorter duration of diabetes were from older patients age 40.8 ± 10.7, 37.7 ± 12.1, 37.1 ± 10.8 years for groups 0-5, 6-10, or >10 years respectively, p <0.001. <h3>Conclusion</h3> Duration of diabetes among donors had no impact on 60 month post-transplant survival. This suggests that the duration of diabetes should not impact donor selection.

Relation of Prolonged Pacemaker Dependency After Cardiac Surgery to Mortality

Permanent pacemaker implantation (PPI) represents a rare complication after cardiac surgery, with no uniform agreement on timing and no information on follow-up. A multicenter retrospective study was designed to assess pacemaker dependency (PMD) and long-term mortality after cardiac surgery procedures. Between 2004 and 2016, PPI-patients from 18 centers were followed. Time-to-event data were evaluated with semiparametric regression Cox models and semiparametric Fine and Gray model for competing risk framework. Of 859 (0.90%) PPI-patients, 30% were pacemaker independent (PMI) at 6 months. PMD showed higher mortality compared with PMI (10-year survival 80.1% ± 2.6% and 92.2% +2.4%, respectively, log-rank p-value < 0.001) with an unadjusted hazard ratio for death of 0.36 (95% CI 0.20 to 0.65, p< 0.001 favoring PMI) and an adjusted hazard ratio of 0.19 (95% CI 0.08 to 0.45, p< 0.001 with PMD as reference). Crude cumulative incidence function of restored PMI rhythm at follow-up at 6 months, 1 year and 12 years were 30.5% (95% CI 27.3% to 33.7%), 33.7% (95% CI 30.4% to 36.9%) and 37.2% (95% CI 33.8% to 40.6%) respectively. PMI was favored by preoperative sinus rhythm with normal conduction (SR) (HR 2.37, 95% CI 1.65 to 3.40, p< 0.001), whereas coronary artery bypass grafting and aortic valve replacement were independently associated with PMD (HR 0.63, 95% CI 0.45 to 0.88, p = 0.006 and HR 0.807, 95% CI 0.65 to 0.99, p = 0.047 respectively). Time-to-implantation was not associated with increased rate of PMI. Although 30% of PPI-patients are PMI after 6 months, PMD is associated with higher mortality at long term.

Pulmonary Metastasectomy in Colorectal Cancer: updated analysis of 93 randomized patients - control survival is much better than previously assumed.

AimLung metastases from colorectal cancer are resected in selected patients in the belief that this confers a significant survival advantage. It is generally assumed that the 5‐year survival of these patients would be near zero without metastasectomy. We tested the clinical effectiveness of this practice in Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC), a randomized, controlled noninferiority trial.MethodMultidisciplinary teams in 14 hospitals recruited patients with resectable lung metastases into a two‐arm trial. Randomization was remote and stratified according to site, with minimization for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, number of metastases and carcinoembryonic antigen level. The trial management group was blind to patient allocation until after intention‐to‐treat analysis.ResultsFrom 2010 to 2016, 93 participants were randomized. These patients were 35–86 years of age and had between one and six lung metastases at a median of 2.7 years after colorectal cancer resection; 29% had prior liver metastasectomy. The patient groups were well matched and the characteristics of these groups were similar to those of observational studies. The median survival after metastasectomy was 3.5 (95% CI: 3.1–6.6) years compared with 3.8 (95% CI: 3.1–4.6) years for controls. The estimated unadjusted hazard ratio for death within 5 years, comparing the metastasectomy group with the control group, was 0.93 (95% CI: 0.56–1.56). Use of chemotherapy or local ablation was infrequent and similar in each group.ConclusionPatients in the control group (who did not undergo lung metastasectomy) have better survival than is assumed. Survival in the metastasectomy group is comparable with the many single‐arm follow‐up studies. The groups were well matched with features similar to those reported in case series.

Low-cost oral metronomic versus intravenous chemotherapy in recurrent, inoperable and metastatic head and neck cancer: Phase III Metro-CIS study.

6506 Background: The NCCN preferred regimens for palliation in head and neck cancer, either EXTREME or KEYNOTE-048 are the only two regimens which have improved outcomes over chemotherapy, but they have limited applicability (1-3%) in low and middle-income countries due to the cost. Oral metronomic chemotherapy (OMC) has shown better outcomes than intravenous cisplatin; these results were obtained with a low incidence of adverse events and the cost of 1/100th of NCCN-preferred regimens in a Phase II study. Methods: This was a randomized Phase III non-inferiority open-label study. Adult patients with relapsed-recurrent or metastatic upfront palliatively treated squamous cell carcinoma of head and neck and ECOG PS 0-1 were eligible. Patients were randomized 1:1 between OMC (oral methotrexate 15 mg/m2 weekly with celecoxib 200 mg once daily or intravenous cisplatin (IVC) 75 mg/m2, 3-weekly for 6 cycles. CTCAE version 4.0 was used for adverse event recording. Response assessment (RECIST version 1.1) was performed every 2 months. EORTC QLQ-C 30 and EORTC QLQ -H&amp;N 35 questionnaires were self-administered at baseline and 2-monthly thereafter. The primary endpoint was overall survival (OS) and was measured from the date of randomization to death. Assuming a 6-month OS in IVC arm of 40%, the non-inferiority margin of 13%, type 1 error of 5% (2-sided), type 2 error of 20% and lost-to-follow up rate of 20%, a total sample size of 422 subjects was required. Kaplan Meier method was used for the estimation of OS and progression-free survival (PFS). To determine non-inferiority the upper limit of 95% CI of difference between 6 months OS of the 2 arms had to be below 13%. Results: In the intention to treat analysis, the 6-months OS was 50.89% (95% CI, 43.3-57.97) and 62.26% (95% CI, 54.72-68.9) in the IVC and OMC arm respectively. The difference in 6-months OS between the 2 arms was - 11.37% (95% CI, -20.77 to -0.97). The median OS was 6.1 (95% CI, 5.33-6.93) versus 7.5 (95% CI, 6.5-8.8) months in IVC arm and OMC arm respectively ( P= .026). The unadjusted hazard ratio for death was 0.773 (95% CI, 0.615-0.97, P= .026). The median PFS was 1.67 (95% CI, 1.47-2.03) versus 3.23 (95% CI, 2.57-4.13) months in IVC and OMC arms respectively ( P&lt; 0.001). Any grade 3 or above adverse events were seen in 61 (30.2%) versus 37 (18.9%) patients in IVC and OMC arm respectively ( P= .01). Conclusions: OMC improves outcomes in palliatively treated head and neck cancer and is a new standard of care in this setting, in addition to the EXTREME and KEYNOTE-048 regimen. Clinical trial information: CTRI/2015/11/006388 .

Relationship among body mass index, NT-proBNP, and mortality in decompensated chronic heart failure

BackgroundObesity has been suggested to confer a survival benefit in acute heart failure. The concentrations of NT-proBNP may be reduced in patients with high body mass index (BMI). ObjectivesTo investigate the relationship among BMI, NT-proBNP, and mortality risk in decompensated chronic heart failure (DCHF). MethodsThis was a retrospective study. We studied 1001 patients with DCHF. Hazard ratios (HR) were calculated with Cox regression analysis. ResultsDuring the 1-year follow-up, 295 patients died. Compared with normal-weight patients, the unadjusted HR for death were 1.02 (95% CIs 0.79–1.33; p = 0.862) for patients with a BMI of 25.0–29.9 kg/m2 and 0.83 (95% CIs 0.61–1.12; p = 0.213) for patients with a BMI ≥ 30 kg/m2. NT-proBNP remained independently associated with mortality across the BMI categories. There was no statistically significant interaction between BMI and NT-proBNP levels for risk prediction. ConclusionsObesity was not associated with mortality risk. NT-proBNP remained an independent prognostic factor across the BMI categories.

Patient-Reported Outcomes Associated with Different Treatments for Myelodysplastic Syndromes

Background: The myelodysplastic syndromes (MDS) are associated with shortened overall survival (OS) and inferior quality of life (QOL). Age, degree of comorbidity, MDS risk group, and treatment status are all likely predictors of both outcomes. We aimed to assess the association between treatment status and patient-reported QOL in a large cohort of community-treated MDS patients at the time of presentation to tertiary care, while controlling for the other three factors.Methods: Beginning in 2006, patients with MDS presenting for their first evaluation at Dana-Farber Cancer Institute (DFCI) were enrolled into a clinical database (consent rate 85%). Enrollment included administration of the EORTC QLQ-C30 (Aaronson, JNCI, 1993), a 30-item measure of QOL that includes subscales for global health (higher score better), fatigue (lower score better), and physical function (higher score better). Medical record review was performed to characterize baseline demographic, clinical, and laboratory data. Treatment status included therapies received in the community during the 30 days prior to QOL assessment, as these were most likely to directly impact QOL. Comorbidity was assigned via the Modified Charlson Comorbidity Index (mCCI; Charlson, Journal Clinical Epi, 1994). MDS prognostic group was assigned via the IPSS-R (Greenberg, Blood, 2012). Associations between treatment status and QOL scores were analyzed with separate multivariable linear regressions adjusted for age, sex, comorbidity, and IPSS-R.Results: In total, 287 patients with complete QLQ-C30 data were included, of which 22% were IPSS-R very high risk, 24% high risk, 22% intermediate risk, 26% low risk, and 6% very low risk. The majority of patients (66%) were male, median age was 68 years, and the mCCI was 0 in 40%, 1-2 in 35%, and 3+ in 24%. Relative to very low risk on the IPSS-R, the unadjusted hazard ratios for death were 1.5 for low risk, 2.2 for intermediate risk, 4.9 for high risk, and 7.2 for very high risk (Ptrend<0.001). In the 30 days prior to tertiary center evaluation, 52% of patients had received therapy: 40% red cell or platelet transfusions, 18% erythropoiesis-stimulating agents (ESAs), 11% either azacitidine or decitabine (HMA), 2.8% lenalidomide, and 2.8% deferasirox (treatments not mutually exclusive). Patients with higher risk disease on the IPSS-R were more likely to have received at least one treatment (41% for very low/low risk, 44% for intermediate risk, 57% for high risk, and 72% for very high risk; Ptrend<0.001). Associations between MDS therapies and QOL adjusted for age, sex, comorbidity, and IPSS-R are shown in the Table. Patients receiving any treatment in the 30 days prior to DFCI presentation experienced inferior global health and physical function, and increased fatigue in comparison to patients receiving no treatment. For patients with anemia, patients receiving an ESA without red cell transfusion experienced superior global health and physical functioning, and less fatigue compared to patients receiving transfusions (and no ESA). Patients receiving an HMA did not have significant differences in QOL compared to those who were not.Conclusions: These data suggest that patients receiving MDS treatments have inferior QOL when compared to patients who are not treated, indicating a need for agents that better address the negative impact of MDS on QOL. Our results encourage the prospective study of the impact of different treatments, established and in development, on QOL. Our data also support the practice of an ESA trial before initiation of transfusions for MDS-related anemia, as the latter was associated with worse QOL even after adjustment for IPSS-R which includes degree of cytopenias. Finally, these results complement a recent report of minimal improvement in OS with HMA treatment in clinical practice (Zeiden, Leukemia and Lymphoma, 2016), suggesting that such treatment may also not be associated with significantly better QOL. [Display omitted] DisclosuresSteensma:Amgen: Consultancy; Genoptix: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Millenium/Takeda: Consultancy; Ariad: Equity Ownership. Stone:Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; Pfizer: Consultancy; Merck: Consultancy; Xenetic Biosciences: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; ONO: Consultancy; Agios: Consultancy; Seattle Genetics: Consultancy; Celator: Consultancy; Jansen: Consultancy; Roche: Consultancy; Sunesis Pharmaceuticals: Consultancy; Karyopharm: Consultancy; Juno Therapeutics: Consultancy. DeAngelo:Novartis: Consultancy; Baxter: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Incyte: Consultancy; Ariad: Consultancy.

Heart Failure with Recovered Ejection Fraction in a Cohort of Elderly Patients with Chronic Heart Failure

Objective: The aim of this study was to determine whether patients with heart failure (HF) who recover left ventricular ejection fraction (LVEF), termed here as ‘Rec-HF', have a distinct clinical profile and prognosis compared with patients with HF and reduced LVEF (HF-REF) or HF and preserved LVEF (HF-PEF). Methods: We evaluated and classified patients from the Spanish Heart Failure Registry into three categories based on enrollment/follow-up echocardiograms: HF-PEF (LVEF ≥50%), HF-REF (LVEF persistently <50%) and Rec-HF (LVEF on enrollment <50% but normalized during follow-up). Results: A total of 1,202 patients were included, 1,094 with HF-PEF, 81 with HF-REF and 27 with Rec-HF. The three groups included patients of advanced age (mean age 75 years) with comorbidities. Rec-HF patients were younger, with a better functional status, lower prevalence of diabetes mellitus, dementia and cerebrovascular disease, and higher prevalence of COPD. The etiology of HF was more frequently ischemic and alcoholic and less frequently hypertensive. After a median follow-up of 367 days, the unadjusted hazard ratios for death in the Rec-HF versus HF-PEF and HF-REF groups were 0.11 (95% CI 0.02-080; p = 0.029) and 0.31 (95% CI 0.04-2.5; p = 0.274). Results were statistically nonsignificant in multivariate-adjusted models. Conclusion: Rec-HF is also present in elderly patients with HF but it is necessary to further investigate the natural history and optimal pharmacologic management of this ‘new HF syndrome'.

Association between strict blood pressure control during chronic kidney disease and lower mortality after onset of end-stage renal disease

There is controversy regarding whether strict blood pressure control is indicated in chronic kidney disease (CKD) since the primary results of randomized controlled trials failed to show any impact on progression of kidney disease with this strategy. However, strict blood pressure control may have other beneficial effects beyond reducing risk of end-stage renal disease (ESRD), such as lowering mortality after ESRD onset. The Modification of Diet in Renal Disease (MDRD) trial randomized 840 patients with CKD to strict (mean arterial pressure under 92 mm Hg) versus usual (mean arterial pressure under 107 mm Hg) blood pressure control between 1989–1993. Here we extended follow-up of study enrollees by linkage with United States Renal Data System and National Death Index to ascertain ESRD and vital status through 2010. Overall, 627 patients developed ESRD through 2010 with median follow-up of 19.3 years. After ESRD onset, there were 142 deaths in the strict blood pressure arm and 182 deaths in the usual blood pressure arm (significant unadjusted hazard ratio for death 0.72 (95% CI 0.58–0.89)). Overall, there were 212 deaths in the strict blood pressure control arm and 233 deaths in the usual arm (significant unadjusted hazard ratio for death 0.82 (95% CI 0.68–0.98)). Thus, although strict blood pressure control did not delay progression of CKD to ESRD, this strategy was associated with a lower risk of death after ESRD. Hence, long-term post-ESRD outcomes should be considered when formulating blood pressure targets for CKD.

EG-11 * DYSREGULATION OF MGMT IN GLIOBLASTOMA: FRIEND OR FOE?

Glioblastoma (GBM) is the most common and lethal form of brain cancer (median survival <15 months). The DNA alkylating agent, temozolomide, is used as the standard chemotherapeutic agent, resulting in mispairing of guanine with thymidine that leads to cellular arrest. However, in GBM patients the O6-methylguanine-DNA methyltransferase (MGMT) protein protects DNA from damage induced by temozolomide. Nevertheless, loss of MGMT expression is a frequent event in human malignancies and typically the result of MGMT promoter methylation. MGMT methylation has been strongly associated with the T-allele of the rs16906252 SNP (C/T) in colorectal carcinoma, pleural mesothelioma, and lung cancers. We therefore examined the T-allele and MGMT methylation in temozolmide-treated GBM patients. In 255 temozolomide-treated GBM patients, we found that the T-allele was significantly more frequent in patients with a methylated MGMT promoter. The unadjusted hazard ratio for death in carriers of the T-allele compared to wild-type, irrespective of methylation status, was 0.39 (95%CI:0.21-0.73; p = 0.003), indicating a 61% relative reduction in the risk for death of T-allele carriers. Surprisingly, GBM patients harboring the T-allele in the absence of MGMT methylation showed a survival benefit comparable to those with MGMT methylation (median survival: 15.5 months) and significantly better than the median survival of wild-type, unmethylated patients (median survival: 10.3 months). This suggests that the T-allele may reduce MGMT activity by mechanisms independent of methylation. Genotyping of 451 healthy controls indicated the frequency of carriage of the T-allele was 13% (MAF 0.065). In contrast, carriage of the T-allele in 160 GBM patients was 17%. Significantly, elevated risks were associated with carriage of the T-allele and development of GBM (odds ratio of 2.62 [95%CI:1.7-4.2]). We report that the T-allele (rs16906252) has predictive (response to temozolomide) and prognostic value (MGMT methylation and longer survival), but conversely may be a predisposing factor for the development of GBM.

Is it possible to define an optimal time for chemotherapy after surgery for ovarian cancer?

ObjectiveThe aims of this study are to investigate the actual time from primary surgery for epithelial ovarian cancer (OC) to initiation of chemotherapy (TI) amongst Danish women in 2005–2006, and to compare the survival for groups with early initiation (≤median TI) and late initiation of adjuvant chemotherapy (>median TI). MethodsAll Danish women who underwent surgery for OC in the period 1 January 2005 to 31 December 2006 and recorded in the Danish Gynaecological Cancer Database (DGCD) were included. The five-year survival was estimated overall and by TI exposure. The Cox proportional hazard regression analysis was used to compute the adjusted hazard ratio (HR). ResultsThe median TI was 32days (25–75% quartile: 24days; 41days). The strongest prognostic factors for death were residual tumour and the International Federation of Obstetrics and Gynecology (FIGO) stage.The unadjusted HR for death in patients with TI>32days compared with TI≤32days was 0.85 (95% CI: 0.70; 1.04), p-value 0.12. When adjusted for residual tumour and FIGO-stage the HR was 1.13 (95% CI: 0.92; 1.39), p-value 0.26. The overall five-year survival was 42.8%, (95% CI: 38.9%; 46.5%). ConclusionsThis nationwide population-based cohort study revealed a non-significant increased risk of death for patients with TI>32days compared with the reference TI≤32days. The strongest prognostic factors were residual tumour after surgery and FIGO-stage. The overall five-year survival was 42.8% (95% CI: 38.9%; 46.5%).

Radiation Therapy Improves Survival in Small Cell Rectal Cancer: Analysis of Surveillance, Epidemiology, and End Results (SEER) Data

Purpose/Objective(s): Small cell rectal cancer is a rare entity with scant literature to guide treatment. We used SEER data to investigate the role of radiation therapy (RT) in the management of this unusual cancer. Materials/Methods: The SEER database (National Cancer Institute) was queried using software for cases of small cell rectal cancer. Locoregional cases were defined using the “SEER Historic Stage A” variable to exclude patients with distant metastatic disease. Years of diagnosis were limited to 1988-2009 to reduce variability in staging criteria or longitudinal changes in surgery and radiation techniques. Two month conditional survival was applied to minimize bias by excluding patients who did not survive long enough to receive cancer-directed therapy. Overall survival was compared between patients who received RT (RT) and those who did not (No_RT) using the Kaplan-Meier method. Multivariate Cox proportional hazards model was used to evaluate important covariates, with AJCC Stage as a stratification variable. Case data were extracted and analyzed. Results: A total of 70 cases of locoregional small cell rectal cancer met the study criteria, No_RT Z 29 and RT Z 41. There were 23 deaths in each group. Median survival was significantly longer for patients who received radiation (RT 30 months vs No_RT 9 months, log-rank p Z 0.003). This corresponded to a higher 2-year overall survival rate for those who received radiation (56.8% vs 23.2%). Unadjusted hazard ratio for death (HR) was 0.43 with the use of radiation (95% CI, 0.24-0.76). Cox proportional hazards model (see Table) identified radiation therapy as the only significant factor for overall survival, multivariate HR Z 0.30 (95% CI, 0.150.62; p Z 0.001). Age, surgery and sex were not significant covariates. Conclusions: Small cell rectal cancer is a rare disease with no proven standard of care. Using the SEER data, we have identified a significant survival advantage with the use of radiation therapy. No survival benefit was seen with surgical resection, although this study lacked power to exclude small to moderate differences. Known limitations of the SEER data apply to this study, especially the lack of information on chemotherapy usage. Our findings strongly support the use of radiation therapy for patients with locoregional small cell rectal cancer. Author Disclosure: H.C. Hsu: None. C.G. Leichman: None. K.L. Du: None.

Long-Term Survival of Participants in the Prostate Cancer Prevention Trial

BackgroundIn the Prostate Cancer Prevention Trial (PCPT), finasteride significantly reduced the risk of prostate cancer but was associated with an increased risk of high-grade disease. With up to 18 years of follow-up, we analyzed rates of survival among all study participants and among those with prostate cancer.MethodsWe collected data on the incidence of prostate cancer among PCPT participants for an additional year after our first report was published in 2003 and searched the Social Security Death Index to assess survival status through October 31, 2011.ResultsAmong 18,880 eligible men who underwent randomization, prostate cancer was diagnosed in 989 of 9423 (10.5%) in the finasteride group and 1412 of 9457 (14.9%) in the placebo group (relative risk in the finasteride group, 0.70; 95% confidence interval [CI], 0.65 to 0.76; P<0.001). Of the men who were evaluated, 333 (3.5%) in the finasteride group and 286 (3.0%) in the placebo group had high-grade cancer (Gleason score, 7 to 10) (relative risk, 1.17; 95% CI, 1.00 to 1.37; P=0.05). Of the men who died, 2538 were in the finasteride group and 2496 were in the placebo group, for 15-year survival rates of 78.0% and 78.2%, respectively. The unadjusted hazard ratio for death in the finasteride group was 1.02 (95% CI, 0.97 to 1.08; P=0.46). Ten-year survival rates were 83.0% in the finasteride group and 80.9% in the placebo group for men with low-grade prostate cancer and 73.0% and 73.6%, respectively, for those with high-grade prostate cancer.ConclusionsFinasteride reduced the risk of prostate cancer by about one third. High-grade prostate cancer was more common in the finasteride group than in the placebo group, but after 18 years of follow-up, there was no significant between-group difference in the rates of overall survival or survival after the diagnosis of prostate cancer. (Funded by the National Cancer Institute.)

Low-risk lifestyle, coronary calcium, cardiovascular events, and mortality: results from MESA.

Unhealthy lifestyle habits are a major contributor to coronary artery disease. The purpose of the present study was to investigate the associations of smoking, weight maintenance, physical activity, and diet with coronary calcium, cardiovascular events, and mortality. US participants who were 44-84 years of age (n = 6,229) were followed in the Multi-Ethnic Study of Atherosclerosis from 2000 to 2010. A lifestyle score ranging from 0 to 4 was created using diet, exercise, body mass index, and smoking status. Coronary calcium was measured at baseline and a mean of 3.1 (standard deviation, 1.3) years later to assess calcium progression. Participants who experienced coronary events or died were followed for a median of 7.6 (standard deviation, 1.5) years. Participants with lifestyle scores of 1, 2, 3, and 4 were found to have mean adjusted annual calcium progressions that were 3.5 (95% confidence interval (CI): 0.0, 7.0), 4.2 (95% CI: 0.6, 7.9), 6.8 (95% CI: 2.0, 11.5), and 11.1 (95% CI: 2.2, 20.1) points per year slower, respectively, relative to the reference group (P = 0.003). Unadjusted hazard ratios for death by lifestyle score were as follows: for a score of 1, the hazard ratio was 0.79 (95% CI: 0.61, 1.03); for a score of 2, the hazard ratio was 0.61 (95% CI: 0.46, 0.81); for a score of 3, the hazard ratio was 0.49 (95% CI: 0.32, 0.75); and for a score of 4, the hazard ratio was 0.19 (95% CI: 0.05, 0.75) (P < 0.001 by log-rank test). In conclusion, a combination of regular exercise, healthy diet, smoking avoidance, and weight maintenance was associated with lower coronary calcium incidence, slower calcium progression, and lower all-cause mortality over 7.6 years.

S92 Risk Factors and Outcome For Emergency Presentation in Lung Cancer Patients

IntroductionThe National Cancer Intelligence Network recently published an analysis of 226,000 cases of cancer and showed that 23% of all cancers had an emergency presentation as their “route to diagnosis”....

Risk Factors for Death in 632 Patients with Sickle Cell Anemia in the United States and United Kingdom

AbstractAbstract ▪3240▪This icon denotes a clinically relevant abstractThe role of pulmonary hypertension as a common and attributable cause of mortality in patients with sickle cell disease remains controversial. To assess this question and explore risk factors for death in patients with sickle cell disease we evaluated 632 patients in the Walk-PHASST pulmonary hypertension screening cohort, recruited from nine different study sites in the United States and one site in the United Kingdom. Methods:Patient characteristics and their associations with mortality were analyzed with Cox proportional hazards regression analysis. Based on data from three right heart catheterization screenings studies that have recently been published, we defined the presence of pulmonary hypertension for this analysis by a Doppler-echocardiographic measurement of the tricuspid regurgitant jet velocity (TRV) ≥ 3.0 m/s, which has a 67–75% positive predictive value for a mean pulmonary artery pressure ≥ 25 mm Hg by right heart catheterization. This therefore represents a very conservative threshold for a large population screening study. Among subjects with a measurable TRV (n=572), 64 (11.2%) had measurements of ≥ 3.0 m/sec. Among those with measurable NT-proBNP (n=582), 140 (24.1%) had measurements ≥160 pg/mL, a value associated with both pulmonary hypertension and mortality. A total of 39 (7.4%) had both high TRV (≥3.0 m/sec) and high NT-proBNP (≥160 pg/mL). Results:Over a median follow-up time of 29 months, we observed 22 deaths. 50% (N=11) of these patients had a TRV≥ 3.0 m/sec. At 24 months the cumulative survival was 83% for patients with TRV ≥ 3.0 m/sec and 98% for patients with TRV < 3.0 m/sec (p<0.0001). The unadjusted hazard ratios for death were 11.14 (95% CI 4.1–30.1; p<0.0001) for patients with TRV above and below 3.0 m/sec and 4.55 (95% CI 1.8–11.3; p=0.001) for patients with NT-proBNP above and below 160 pg/mL. For patients with both high TRV (≥ 3.0 m/sec) and high NT-proBNP (≥ 160 pg/mL), the unadjusted hazard ratio was 14.86 (95% CI 5.5–39.9; p<0.0001). Overall, an increased risk of death was observed for both age and gender, with males at higher risk relative to females (HR=2.48, 95% CI 1.0–6.1; p=0.05), and patients older than 47 years (HR=2.02, 95% CI 1.1–3.8; p=0.03). Associations with mortality were also observed for chronic transfusions (HR=3.00, 95% CI 1.2–7.8; p=0.02) and a NYHA/WHO class value or III or IV (HR=4.52, 95% CI 1.4–14.3; p=0.01). Other variables associated with mortality in our cohort included a high hemolytic component, aspartate aminotransferase (AST), ferritin, and creatinine. Variables not associated with mortality included current hydroxyurea use, SC disease, self-reported history of painful episodes, and six-minute walk distance. In stepwise multiple proportional hazards regression analysis, the association between TRV and mortality remained significant after adjustment for all other risk factors, including ferritin, AST, creatinine and even NT-proBNP (HR 4.27, 95%CI 1.3–14.1; p=0.04). Conclusions:Using a more conservative cut-off value of TRV ≥ 3.0 m/sec as defining PH in a large screening population of sickle cell disease patients, PH occurs in approximately 10% of unselected screened patients and is associated with the highest unadjusted and adjusted risk for death of any measured variable. Disclosures:Gladwin:Bayer Corp: Consultancy, Research Funding; NIH and NHLBI: Research Funding; Gilead Sciences: Research Funding. Barst:Ventripoint: Stock options Other; Actelion, Eli Lilly, Gilead, Glaxo Smith-Kline (GSK), Medtronics, Bayer, Ikaria, Pfizer, Novartis, VentriPoint: Consultancy, Honoraria. Girgis:NIH/NHLBI: Research Funding, Travel support Other. Rosenzweig:NIH: Research Funding. Badesch:NIH: Research Funding. Lanzkron:NIH: Research Funding.

Abandoning Peracetic Acid-Based Dialyzer Reuse Is Associated with Improved Survival

Higher mortality risk reported with reuse versus single use of dialyzers is potentially related to reuse reagents that modify membrane surface characteristics and the blood-membrane interface. A key mechanism may involve stimulation of an inflammatory response. In a prospective crossover design, laboratory markers and mortality from 23 hemodialysis facilities abandoning reuse with peracetic acid mixture were tracked. C-reactive protein (CRP), white blood cell (WBC) count, albumin, and prealbumin were measured for 2 consecutive months before abandoning reuse and subsequently within 3 and 6 months on single use. Survival models were utilized to compare the 6-month period before abandoning reuse (baseline) and the 6-month period on single use of dialyzers after a 3-month "washout period." Patients from baseline and single-use periods had a mean age of approximately 63 years; 44% were female, 54% were diabetic, 60% were white, and the mean vintage was approximately 3.2 years. The unadjusted hazard ratio for death was 0.70 and after case-mix adjustment was 0.74 for single use compared with reuse. Patients with CRP≥5 mg/L during reuse (mean CRP=26.6 mg/ml in April) declined on single use to 20.2 mg/L by August and 20.4 mg/L by November. WBC count declined slightly during single use, but nutritional markers were unchanged. Abandonment of peracetic-acid-based reuse was associated with improved survival and lower levels of inflammatory but not nutritional markers. Further study is needed to evaluate a potential link between dialyzer reuse, inflammation, and mortality.

Risk factors for developing a new venous thromboembolism in ambulatory patients with non-hematologic malignancies and impact on survival for gastroesophageal malignancies.

Venous thromboembolism(VTE) is a significant, common comorbidity of cancer patients associated with increased mortality. We evaluated the incidence and risk factors for developing a new VTE in ambulatory cancer patients while they were receiving therapy for advanced cancer. We also examined the affect of developing a new VTE on survival for patients with gastroesophageal malignancies. All patients with non-hematologic malignancies who were treated using investigator-initiated therapeutic protocols at Memorial Sloan Kettering Cancer Center (MSKCC) from 2003 through to 2005 were identified for this cohort study. The occurrence of VTE was prospectively recorded in an actively managed clinical research database. Baseline laboratory parameters, treatment details and tumor type were correlated with VTE risk and patient survival. 115 out of 2120 patients being treated for advanced malignancy developed a new VTE (12.8 VTEs/100 person-years). In multivariate analysis, a diagnosis of gastroesophageal cancer (hazard ratio (HR), 2.76 (1.41-5.38); P=0.003), pancreatic cancer (HR, 2.26 (1.06-4.80); P=0.05), use of white cell growth factors (HR 1.69(1.09-2.64); P=0.02) and irinotecan therapy (HR, 1.89 (1.29-3.59); P=0.05) were independently associated with VTE development. Hemoglobin >10 g dL(-1) (HR, 0.52 (0.3-0.91); P=0.02) and albumin ≥ 4 g dL(-1) (HR, 0.61 (0.39-0.94); P=0.024) were associated with reduced VTE risk. The unadjusted HR for death among ambulatory gastroesophageal cancer patients with VTE is 0.89 (0.61-1.3), P=0.53. After adjusting for confounding risk factors associated with survival, the HR for death associated with VTE is 0.78 (0.5-1.2), P=0.25. Upper gastrointestinal malignancies are independently associated with the development of a new VTE, implicating tumor biology in VTE development. Even after adjusting for prognostic factors, we were unable to demonstrate an adverse impact on survival due to the new development of VTE amongst patients with active gastroesophageal malignancy receiving therapy.

Survival After Bilateral Versus Single-Lung Transplantation for Idiopathic Pulmonary Fibrosis

Patients with end-stage idiopathic pulmonary fibrosis (IPF) are increasingly having bilateral rather than single-lung transplantation. To compare survival after single and bilateral lung transplantation in patients with IPF. Analysis of data from the United Network of Organ Sharing registry. Transplantation centers in the United States. 3327 patients with IPF who had single (2146 patients [64.5%]) or bilateral (1181 patients [35.5%]) lung transplantation between 1987 and 2009. Survival times and causes of death after lung transplantation. Selection bias was accounted for by multivariate risk adjustment, propensity score risk adjustment, and propensity-based matching. Median survival time was longer after bilateral lung transplantation than single-lung transplantation (5.2 years [CI, 4.3 to 6.7 years] vs. 3.8 years [CI, 3.6 to 4.1 years]; P < 0.001). However, survival times for the 2 procedures did not differ after adjustment for baseline differences, with adjusted hazard ratios (HRs) for mortality with bilateral transplantation ranging from 0.89 (95% CI, 0.79 to 1.02) to 0.96 (CI, 0.77 to 1.20) in different analyses. Bilateral lung transplantation seemed to result in harm within the first year (HR, 1.18 [CI, 0.98 to 1.42]) but survival benefit thereafter (HR, 0.72 [CI, 0.59 to 0.87]). Primary graft failure was a more common cause of death among patients who had bilateral rather than single-lung transplantation (3.7% vs. 1.9%; P = 0.002). Cancer was a more common cause of death among patients who had single rather than bilateral lung transplantation (unadjusted HR for death among single vs. bilateral transplant recipients, 3.60 [CI, 2.16 to 6.05]; P <0.001). Causes of death were ascertained without an adjudication committee and must be interpreted cautiously. Survival did not differ between patients who had single and bilateral lung transplantation. Single-lung transplantation confers short-term survival benefit but long-term harm, whereas bilateral transplantation confers short-term harm but long-term survival benefit. None.

Neopterin as a Predictor of Total and Cardiovascular Mortality in Individuals Undergoing Angiography in the Ludwigshafen Risk and Cardiovascular Health Study

Neopterin is produced upon activation of the cell-mediated immune response, and may be a novel risk marker for adverse outcomes resulting from coronary artery disease. We measured neopterin in 1801 study participants with and 511 without angiographic coronary artery disease. Rates of death were determined after a median follow-up of 8.0 years. Estimated glomerular filtration rate and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were the strongest predictors of neopterin. Neopterin was positively related to age and inversely related to LDL cholesterol, HDL cholesterol, and triglycerides. Use of lipid-lowering drugs lowered neopterin. Sex, body mass index, diabetes mellitus, hypertension, smoking status, Friesinger coronary score, and clinical instability at presentation were not associated with neopterin. Unlike C-reactive protein, neopterin was not increased in unstable angina pectoris, non-ST-elevation myocardial infarction, or ST-elevation myocardial infarction. In the third and fourth quartiles of neopterin, unadjusted hazard ratios for death from any cause were 1.94 (95% CI 1.44-2.61) and 3.32 (95% CI 2.53-4.30) compared to individuals in the first quartile, whereas hazard ratios for death from cardiovascular causes were 2.14 (95% CI 1.44-3.18) and 3.84 (95% CI 2.67-5.52), respectively. Neopterin remained predictive of total and cardiovascular mortality after adjusting for sex, age, body mass index, type 2 diabetes, hypertension, smoking status, LDL cholesterol, HDL cholesterol, triglycerides, estimated glomerular filtration rate, NT-proBNP, and clinical status at presentation, but NT-proBNP substantially weakened this association. Neopterin is an independent predictor of all-cause and cardiovascular mortality in individuals with or without stable coronary artery disease.